The products obtained according to this invention consist respectively of the carbonyl compound hydrogenated to alcohol or of the alcohol dehydrogenated to ketone, or to aldehyde.
This invention, in fact, though described as being specifically directed to the preparation of alcohols according to the abovesaid technology, can be considered, of course, as effective for obtaining ketonic compounds (aldehydes or ketones) from alcohols.
According to a particular aspect of this invention, it is possible to obtain, through said hydrogen transfer reaction, optically active alcohols starting from prochiral ketones.
The products obtained can be usefully employed in a wide field of industrial applications. In fact, they represent active intermediates for organic syntheses in general, with particular possibilities in the field of fine chemicals.
For many of them, the industrial applications are disclosed in literature; for example it is possible to prepare cyclohexanol from cyclohexanone and derivatives thereof, which are interesting compounds in the field of the insecticides, of celluloid, solvents for rubbers, resins, etc., .alpha.-phenylethanol from acetophenone for dyes, perfumes, etc.
By the method forming the object of this invention it is possible to obtain, in particular, selective reductions of steroids having carbonyl groups, which are of particular interest in the pharmaceutical field.
For example, from dehydro-epi-androsterone acetate it is possible to obtain the corresponding reduction product of the carbonyl group in position 17.
Methods of preparing alcohols by catalytically transferring a hydrogen atom from a molecule of a primary or secondary alcohol to a molecule of a ketone or of an aldehyde are known.
The reaction results more or less shifted in the desired direction depending on the parameters. Generally it is best operated by using isopropanol as the alcohol donor, due to the facility of separating the acetone deriving from dehydrogenation.
It is known how to use aluminium alkoxides (Meerwein-Ponndorf reaction), but the necessity of operating with a practically stoichiometric ratio renders the proposed method uninteresting from an industrial viewpoint.
Other described catalysts can lead to heterogeneous systems, such as by employing potassium hexachlororuthenate precipitated with sodium formate, and in such case they exhibit the drawbacks which are typical of the reactions in a heterogeneous phase (shorter life of the catalyst, etc.).
Catalyst systems which may permit to operate a homogeneous phase have therefore been studied.
They are essentially based on the use of complexes of transition metals of Group VIII, among which the most studied ones are those deriving from iridium, ruthenium and rhodium.
Therefore, the complex catalysts of formula:
Ir Cl.sub.3.3DMSO (DMSO=dimethylsulphoxide); Ru Cl.sub.2 [P (C.sub.6 H.sub.5).sub.3 ].sub.3 and Rh[Cl P (C.sub.6 H.sub.5).sub.3 ].sub.3
respectively operating in an acid (HCl), neutral or alkaline, or quite alkaline medium, have been proposed.
Usually, isopropanol or primary alcohols in general, especially benzyl alcohol for the ruthenium catalyst, are described as alcohol donors.
Generally, however, the activity and/or the stereoselectivity obtained in the described substrata, such as the substituted cyclohexanones, is not high. This is a remarkable drawback, since the reaction, as explained hereinbefore, is electively directed to yield fine chemical compounds for which the steric aspect is of the utmost importance. Furthermore, the catalysts described hereinabove provide in general unsatisfactory reaction rates, no doubt lower (even of the order of 100 times) than the ones achievable by using the catalysts according to the present invention, which therefore are remarkably more suitable for industrial uses.
Finally, syntheses of optically active alcohols starting from prochiral ketones through an actual hydrogenation reaction, i.e. a reaction conducted by using molecular hydrogen, have been described.
The reaction is conducted in the presence of rhodium catalysts with chiral binders. Said binders may be phosphines, mono phosphines, diphosphines, ferrocenylphosphines, aminophosphines, diphosphinites, or catalysts based on chiral aminoalcoholic complexes of cobalt are employed.
The catalytic reduction by transfer of hydrogen of an ethylene double bond to .alpha.- or .beta.-unsaturated prochiral ketones which become saturated, with phosphinic complex (achiral) catalysts of rhodium and glucides (chiral), has also been described as an alternative method.
The above-mentioned techniques, however, are not directly pertaining to the present invention, because they either employ molecular hydrogen as a reducing agent, or concern the reduction of double bond C.dbd.C without selectively affecting the carbonyl group.
The complex catalysts of rhodium and of iridium employed according to this invention are compounds known in themselves and described as having catalytic capabilities in hydrogenation reactions, namely in reactions employing molecular hydrogen as a hydrogenating agent, as explained hereinabove. By consequence such technology has no connection with the one utilized in the present invention.
The present invention represents, in a certain manner, an unexpected overcoming of a prejudice existing in the prior art, according to which the rhodium and iridium complex catalysts of the type described hereinbefore not always exhibited a satisfactory selectivity, or it describes the use of such catalysts in actual hydrogenation reactions with gaseous H.sub.2.